Indium generator

ABSTRACT

A GENERATOR OF A DAUGHTER RADIONUCLIDE, PARTICULARLY RADIOACTIVE INDIUM (IN113M), AND A METHOD OF LOADING A PARTICULATE SUBSTRATE OF THE GENERATOR WITH A PARENT RADIONUCLIDE. THE DAUGHTER RADIONUCLIDE, WHICH RESULTS FROM THE RADIOACTIVE DECAY OF ITS PARENT, IS SELECTIVELY EXTRACTED FROM THE SUBSTRATE BY A MINERAL ACID SOOLVENT (ELUANT),   SUCH AS HYDROCHLORIC ACID (HC1) AT A CONCENTRATION LESS THAN ONE-TENTH NORMAL (0.1 N).

Feb. 9, 1971 RUV ET AL 3,561,932

INDIUM GENERATOR Filed Jan 26, 1967 1 I I I F I G. 3

n a. a a a F l G. 4

INVENTORS IRWIN J. GRUVERMAN BYGREGORY G ROCCO 0% 9%amd0z W F I G. 2

ATTORNEYS United States Patent 3,561,932 INDIUM GENERATOR Irwin J.Gruverman, Needham, and Gregory G. Rocco,

Wakefield, Mass., assignors to New England Nuclear Corporation, Boston,Mass., a corporation of Massachusetts Filed Jan. 26, 1967, Ser. No.611,963 Int. Cl. B01d 11/02; C01g 15/00, 19/00 US. Cl. 23-312 4 ClaimsABSTRACT OF THE DISCLOSURE A generator of a daughter radionuclide,particularly radioactive indium (ln and a method of loading aparticulate substrate of the generator with a parent radionuclide. Thedaughter radionuclide, which results from the radioactive decay of itsparent, is selectively extracted from the substrate by a mineral acidsolvent (eluant), such as hydrochloric acid (HCl) at a concentrationless than one-tenth normal (0.1 N).

An appropriate substrate is of zirconium oxide (ZrO in two layers ofdifferent granularity. Flow of the extractive eluant through thesubstrate is regulated by a flow distribution cap, which also holds thesubstrate in place within the generator, and by various porous layersintermediate to the substrate and at its extremities to prevent dryingof the substrate, thus, avoiding channelled flow of the eluant.

The substrate is loaded by depositing the parent radionuclide in theform of radioactive tin (Su as by percolation with an aqueous solutionof hydrochloric acid and tin at a normality between 0.1 and 1.0; washingthe substrate; and repeating the foregoing set of steps, using, for eachsucceeding set of steps, the percolating eflluent used in theimmediately preceding set of steps.

BACKGROUND OF THE INVENTION The present invention relates to thegeneration of radioactive indium (particularly In especially for medicaland industrial scanning and tracing, using radioactive tin (Su over awide range of specific activity as a precursor radionuclide from whichIn is generated by radioactive decay.

Radioactive indium in the form of I11 has certain advantages over otherradioactive scanning and tracing agents, such as T0 I Hg and Hg Forexample, from a medical standpoint, the delivered radiation dosage to apatient is much lower using ln than when using I Hg or Hg while at thesame time In achieves scanning resolution comparable or superior tothese other nuclides. As compared with Tc In has the advantage of ashorter half life, i.e. 1.7 hours as compared with 6.0 hours for Te Thisshorter half life, together with the fact that In radiates no betaparticles, for example as compared with I .and Hg decreases patientradiation dosage. Also, the shorter half life simplifies decontaminationprocedures in the laboratory and hospital and permits radiotracerprocedures to be performed on the patient after a shorter decay intervalthan is the case for any of the above mentioned radionuclides. Further,with respect to the generator itself, this short half life permits morefrequent elution of the In from the generator, as compared for examplewith Tc since the rate at which the daughter (In in one case, and Tc inthe other case) is generated from the parent is controlled primarily bythe half life of the daughter.

Although, because of the lack of beta particles and the short half lifeof In relative to 1 radiation dosage to the patient is decreased,nevertheless, In has an advantage over other replacements for I in thatit emits gamma rays which can be scanned using the same conven tionalequipment used for I This is true because the principal gamma ray energyof I is 364 kev. and that of In is 390 kev. By contrast, the gamma rayenergy of Tc is kev. and requires the use of substantially differentcollimation components of the scanning equipment.

The post-elution chemical procedures for treating the eluted daughter toprepare the final scanning agents are generally simpler for In than theyare for Tc Not only does In offer the aforesaid advantages but, inaddition, an Su -In generator system is highly desirable because Sn hasa relatively long half life of 118 days compared with 67 hours for Mofrom which Tc is generated. A long parent half life is desirable,firstly, because the longer the parent half life, the longer the usefullife of the generator, and secondly, because production and delivery ofthe generator can be carried out on a more convenient schedule. Thus,with a shorter lived parent, shipping and delivery schedules must beclosely observed, with resulting higher costs, to make sure that delaysare minimized. Furthermore, a shorter lived generator must be preparedto order, whereas a long lived generator can be prepared convenientlyfor stock.

All of these advantages make an Su -In generator highly desirable.

Although there have been attempts to provide a commercially useful Sn-In generator system, until the present invention no one hassuccessfully done so.

in order to understand the problems involved in providing such a system,it is necessary to explain the principles of a parent-daughterradionuclide generator of this type. In the conventional form of such agenerator, the parent radionuclide is deposited or fixed on a solidparticulate substrate, e.g. alumina, zirconium oxide, organic ionexchange resins, etc., in the form of a column. The parent is aradionuclide having a relatively long half life and decaying to thedaughter which has a relatively short half life, this relatively shorthalf life being one of its desirable properties as a radioactivescanning agent, but at the same time making its storage and shipmentdiificult. In effect, with the aforesaid generator system, the shelflife of the daughter becomes that of the parent since it is available aslong as the parent is available. When it is desired to use the daughter,it is extracted or eluted from the generator column by passing asolvent, selective to the daughter, through the column. The elutingsolvent must have the property of efficient removal of the daughter fromthe generating column without removal of any significant fraction of theparent. The daughter continues to be generated in the column as long asthe parent remains.

There were a number of major problems in achieving a commerciallysatisfactory Sn ln generator. Firstly, Sn is a costly material and mustbe utilized eificiently in loading the generator in order for cost ofthe generator to be commercially acceptable. Secondly, difficulty wasmet in achieving satisfactorily high yields of In in the eluting fluidwithout substantial leakage of the parent Sn i.e. without the elutingfluid containing unacceptable amounts of the Su Such leakage renders thegenerator unaceptable because the product eluate contains the long livedimpurity, Su thereby making it more dangerous for medical use as well asshortening the life of the generator. Thirdly, difliculties were met indepositing or fixing on the substrate column a sufficient mass of tin toachieve adequate Sn intensities. Fourthly, difficulties were met inpreventing channeling of the eluting solution through the column, whichis undesirable because only a fraction of the column capacity isachieved resulting in low elution yields and reduced tin retentioncapacity. Fifthly, difficulties were met in preventing the column fromdrying between elutions with consequent inconsistencies in elution flowrate and elution etficiencies. Sixthly, difliculties were met inreducing the concentration of dissolved substrate matter in the eluantto acceptable levels. Post elution chemistry is complicated by thepresence of such substrate material.

The present invention provides for the first time a commerciallyacceptable Sn In generator system and method which overcomes all theaforesaid difiiculties.

SUMMARY OF THE INVENTION According to one aspect of the presentinvention, high In yields are achieved in the eluting fluid with minimumleakage of Sn and substrate material, to thereby solve these problems,by using as an eluting fluid, with a zirconium oxide substrate material,an aqueous solution of HCl at a concentration of less than 0.1 N, andpreferably between about 0.02 N and 0.08 N. The most preferred HClconcentration is from about 0.04 N to 0.06 N. Optimum results have beenachieved with an HCl concentration of 0.05 N. Although other acids,particularly mineral acids, such as HNO and HBr can be used in place ofHCl, the latter is highly preferred.

Also, according to another aspect of the present invention, the Su isloaded on the particulate substrate, particularly ZrO to produce the Ingenerator by the steps of 1) contacting the substrate particles with anSn solution to deposit Su on such particles, (2) separating the solutionfrom the particles (preferably steps (1) and (2) are carried out byflowing the solution through a column of the substrate particles), (3)then Washing the particles (preferably by passing a wash solu tionthrough the column) and (4) repeating these steps at least once, butpreferably twice, using as the Sn solution in each repeat of step (1)the spent separated Sn solution from the preceding treatment with Snsolution, to thereby overcome the aforesaid loading difficulty and theaforesaid difiiculty of achieving adequate Su column intensities.Preferably, the Sn is in an aqueous HCl solution having a normality ofless than 1.0 and more than 0.1, preferably, between 0.3 and 0.5, andwhich has been treated with an oxidizing agent, preferably by bubblingchlorine gas through it, and the wash solution is an aqueous HClsolution between 0.02 N and 0.08 N, preferably 0.04 N to 0.06 N.

Also, according to a further aspect of the invention, the generatorcomprises two layers of the particulate substrate, preferably zirconiumoxide particles, the upper layer being relatively coarse and the lowerlayer relatively fine. These layers are separated by a porous,liquid-retaining layer of an inert material, preferably glass Wool,having pores small enough to retain the eluting liquid. The upper coarselayer is covered with a similar liquidretaining layer and the entireassembly is secured within the column container at its bottom by aporous support secured to the container and at its top by a cap securedin the container and having perforations distributed over Sn solution todeposite Sn on each particles, (2) sepdiificulties of channeling due todrying of the coarse substrate and due to nonuniform flow over thecolumn crosssectional area, are overcome.

The objects and advantages of the invention will be apparent from thefollowing description and the accompanying drawings of an illustrativeembodiment of the invention:

BRIEF DESCRIPTION OF THE DRAWINGS In the drawings:

FIG, 1 is an elevational view in section of a radionuclide generatorembodying the invention;

FIG. 2 is a horizontal sectional View along the section line Z-2 of FIG.1 showing a top view of a flow distribution cap;

FIG. 3 is a perspective view of the flow distribution cap shown in FIG.2;

FIG. 4 is a partial sectional and perspective view of a compositeassembly including the generator of FIG. 1 and a shield for thegenerator.

DESCRIPTION OF THE PREFERRED EMBODIMENTS With reference to the drawings,a generator 10 embodying the present invention is constituted of ahollow cylinder 20 of durable and chemically inert composition,desirably glass, which incorporates a radionuclide generator column 30.The cylinder 20 extends from an outwardly flared portion 21 to aconstricted portion 22 taking the form of a spout.

The generator column 30 includes two substrate layers 31 and 32 whichare supported by a porous supporting layer 40. The substrate layers 31and 32 are desirably particles of zirconium oxide (ZrO with the upperlayer 31 being composed of coarser particles than the lower layer 32.The porous support layer 40 is of durable and chemically inertcomposition, being advantageously of fritted glass which is sealed tothe inside wall of the cylinder 20.

Disposed between the two substrate layers 31 and 32 is an intermediatelayer 33 of porous and inert material such as glass wool. At the top ofthe generator column 30 is a further layer 34 of porous and inertmaterial such as glass wool. The column 30 is held in place against thesupport layer 40 by a flow distribution cap 50, which is chemicallyinert with respect to the substances used in conjunction with thegenerator 10, At the same time the cap 50 is flexible so that it willgrip the interior wall of the cylinder 20. Plastic has been found to bea suitable material for the cap 50, which is detailed in FIGS. 2 and 3.

In order to produce the desired daughter radionuclide in the form ofradioactive indium (In the substrate layers 31 and 32 are loaded withthe corresponding parent radionuclide in the form of radioactive tin (SnThe parent decays naturally into its daughter, which is removed from thecolumn 30 by selective extraction with a suitable solvent, i.e. eluant.In the case of In such a solvent is hydrochloric acid with a normalityof less than 0.1 N.

The elution is accomplished using conventional attachments andaccessories for the generator 10 by gravity flow or by forced flow ofthe eluant through the generator 10. By having the upper substrate layer31 of greater coarseness than the lower layer 32, the efficiency of theelution process is enhanced. Since the upper layer 31 is coarser thanthe lower layer 32, there is less resistance to flow through the upperlayer 31. Gravity flow encounters less resistance in the coarse layer 31than in the fine layer 32. However, the pressure head is greater in thefine layer. The result is that uniformity of flow through the overallcolumn is promoted. The fine layer 32 also serves to filter particlesoriginating in the coarse layer. Alternatively, elution may take placeby forcing the eluant upward through the spout 22 into the column 30 andout of the flared portion 21. Again, elution takes place usingconventional accessories.

The eluting fluid wets the substrate during elution. If the residualmoisture of the substrate varies during the various inter-elutionintervals, there is a consequent effect upon the rate of flow of theeluant and upon the efficiency of elution. Flow takes place with greaterrapidity, and hence greater eluting efficiency, to the extent that thesubstrate is wet rather than dry. In addition, the rate of flow is moreuniform for each elution if significant loss of moisture from thesubstrate is prevented during inter-elution intervals. Furthermore,nonuniform drying of the columnar substrate can lead to preferredchannels of flow for the eluant. The result is not only ineflicient useof the substrate but also the possibility of a breakdown by which tracesof the parent Sn are removed from the column in the eluate containingthe desired daughter In The orous layers 33 and 34 of the column 30serve to reduce variations in the amount of moisture retained by thesubstrate, as well as promote uniformity of. flow. To that end bothlayers 33 an 34 are of a porosity which is suitable for the retention ofsuflicient moisture to maintain a satisfactory degree of moistness inthe generating column 30. The intermediate layer 33 reduces the drainageof moisture from the upper substrate layer 31. It also curtailsevaporation from the lower substrate layer 32. Similarly, the upperporous layer 34 curtails the evaporation of moisture from the uppersubstrate layer 31.

In addition, when eluant enters the porous layers 33 and 34, it spreadsover the cross section of the generator column 30. The uniformdistribution of eluant over the cross section of the columnar substrateplays a significant role in avoiding channelling and in promotinguniformity of flow. Uniformity of eluant flow through the generatorcolumn 30 is also promoted by the configuration of the flow distributioncap 50, details of which are set forth in FIGS. 2 and 3.

The retaining cap 50 has an aperture 51 at its center and notches 52 inits periphery. For the particular embodiment shown in the perspectiveview of FIG. 3 there are four uniformly distributed circumferentialnotches 521 through 5 2-4, which extend radially inward along the baseof the cap 50. In addition, the periphery of the cap 50 extends upwardlyinto a compressible resilient rim 53 which frictionally engages theinside wall of the glass container 20, as shown in FIG. 1, to secure thecap and the layers of particulate zirconium oxide and glass wool withinthe generator cylinder 20.

In order for the generator of FIG. 1 to function efficiently, itssubstrate layers are advantageously loaded with a significant mass of SnIn accordance with the invention, a method of loading the substratelayers includes the steps of contacting the substrate particles, as

by percolation, with a solution containing radioactive tin in order todeposit the parent radionuclide. Once the parent has been deposited uponthe substrate particles the flow of depositing solution is terminated,following which the particles are washed by a wash solution in order toremove any residual excess of radioactive tin. The foregoing set ofsteps is repeated at least once, using for each repetition thecontacting tin solution effluent from the preceding set of steps. Byusing the tin solution effiuent a number of times, an adequate loadingof the substrate with the parent radionuclide is establishedcumulatively at a considerable cost saving, as compared with the use ofa fresh contacting solution with each set of steps.

In a tested model of the invention, the radioactive tin of thecontacting solution was in aqueous solution of hydrochloric acid whichhad been treated by bubbling chlorine gas through it. The normality ofthe tin solution ranged from less than 1.0 N to more than 0.1 N, with apreferred range between 0.3 N and 0.5 N. The wash solution was anaqueous solution of hydrochloric acid of normality less than 0.1 N,desirably between 0.02 N and 0.08 N, and preferably in the range from0.04 N to 0.06 N.

For a typical and illustrative column 30 of the generator 10 in FIG. 1,the diameter is approximately 1 inch. In such a column, the coarsesubstrate layer 31 preferably ranges in height from inch to 2 inches,with particles ranging in size from 50 to 100 mesh, as sold and marketedunder the designation Bio-Rad HZO-l Ion Exchange Crystals. The finesubstrate layer .32 preferably ranges in height from A; inch to inch andis composed of particles ranging from 100 to 200 mesh. In general, theheights of the various substrate layers 31 and 32, for a column ofprescribed diameter, depend in part upon the extent to which the columnis to be loaded with the parent radionuclide.

In an illustrative column 30 with a diameter of approximately 1 inch,the porous layers 33 and 34 preferably range in thickness fromapproximately /5 to A of an inch and are desirably of wettableborosilicate fibers in the range from 0.0002 to 0.0003 inch. Such glasswool fibers are commonly available under the designation Corning Number3950. To achieve suitable porosity for the layers 33 and 34 ranging inthickness from approximately /s to A of an inch, the mass of theborosilicate fibers advantageously corresponds to a weight in the rangefrom 200 to 300 milligrams. Suitable porosity for the layers 33 and 34can also be achieved using such Wettable materials as filter cloth andthe like.

For a tested model of the invention, the glass support layer wasconstructed as an integral part of the cylinder 20 and was of acharacter commonly designated in the glass blowing art as coarse fit.The thickness of a tested frit layer 40 was slightly in excess of A ofan inch, being desirably in the range from A to of an inch.

In an illustrative model of the invention, the flow distribution cap hada thickness of approximately of an inch. The cap is advantageously ofany of the common plastics, such as polyethylene, which provide suitableadhesion to the sides of the cylinder 20 in order to provide a frictionfit by which the constituents of the generator column 30 are retained inplace. In one design of the cap 50 the apertures of 52-1 through 52-4and the central aperture 51 were symmetrically arranged and disposed sothat approximately /2 of the cap area was open to the passage of theeluting fluid.

The generator cylinder 20 may be of a suitable plastic,

such as polyethylene. However, the cylinder 20 is advantageously ofrelatively non-porous and inert material such as glass, in which event,it is frangible, and precautions must be taken to prevent breakage. Inany case, it is desirable to protect the cylinder 20 since the generatorcolumn 30 contains radioactive materials when loaded. Accordingly, thecylinder is desirably mounted in a flexible protective shield as shownin FIG. 4. A suitable shield is of plastic which secures the cylinder 20by having the rim of its flared portion 21 resting on the top edge ofthe shield and by having a soft plastic Wedge 61 with the shield andencircling the cylinder 20 near the spout 22. In a test model of theinvention, the shield 60' was illustratively about 7 inches in lengthand about 1 /2 inches in outside diameter, while the cylinder 20'contained by the shield was approximately 1 inch in diameter. In use,the plastic shielded generator 10 of FIG. 4 is generally employed inconjunction with radiation shielding, such as provided by a lead closureor by a leadshielded chamber. However, where the radioactivity of thecolumn 30 is at a suitably low level, the generator 10 may be employedwithout such auxiliary shielding.

Other adaptations of the invention, and techniques of employment, willoccur to those skilled in the art.

We claim:

1. In a method of eluting In from a column consisting of particles ofZr0 substrate upon which Sn is supported, the improvement comprisingeluting said In by passing through said column an aqueous solution ofhydrochloric acid at a concentration below 0.1 N but not less than about0.02 N, whereby high In yields are achieved With minimum leakage of $11and zirconium originating in the zirconium substrate.

2. A method according to claim 1, said concentration of HCl beingbetween 0.02 N and 0.08 N.

3. A method according to claim 1, said concentration of HCl beingbetween 0204 N and 0.06 N.

4. A method according to claim 1, said column being enclosed in aplastic container.

References Cited UNITED STATES PATENTS 8 OTHER REFERENCES Mayer et al.:Ind. and Eng. Chem, vol. 52, N0. 12, December 1960, pp. 993 to 994.

Gillette: ORNL-3802, May 1965, pp. 1 to 3, 8, 9, 11, 12, 14,18, 19.

NORMAN YUDKOFF, Primary Examiner S. J. EMERY, Assistant Examiner U.S.Cl. X.R.

